Alpha1-antitrypsin impacts innate host-pathogen interactions with Candida albicans by stimulating fungal filamentation

被引:3
作者
Jaeger, Martin [1 ,2 ,3 ]
Dietschmann, Axel [4 ]
Austermeier, Sophie [5 ]
Dincer, Sude [4 ]
Porschitz, Pauline [4 ]
Vornholz, Larsen [6 ]
Maas, Ralph J. A. [1 ,7 ]
Sprenkeler, Evelien G. G. [2 ,3 ]
Ruland, Juergen [6 ,10 ,11 ]
Wirtz, Stefan [8 ]
Azam, Tania [1 ]
Joosten, Leo A. B. [2 ,3 ]
Hube, Bernhard [5 ,9 ]
Netea, Mihai G. [2 ,3 ]
Dinarello, Charles A. [1 ,2 ,3 ]
Gresnigt, Mark S. [1 ,4 ]
机构
[1] Univ Colorado Denver, Dept Med, Aurora, CO 80204 USA
[2] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands
[3] Radboud Ctr Infect Dis RCI, Nijmegen, Netherlands
[4] Leibniz Inst Nat Prod Res & Infect Biol, Hans Knoll Inst, Jr Res Grp Adapt Pathogen Strategies, Jena, Germany
[5] Leibniz Inst Nat Prod Res & Infect Biol, Hans Knoll Inst, Dept Microbial Pathogen Mech, Jena, Germany
[6] Ctr Translat Canc Res TranslaTUM, Sch Med & Hlth, Inst Clin Chem & Pathobiochem, Munich, Germany
[7] Radboud Univ Nijmegen, Med Ctr, Dept Lab Med, Lab Hematol, Nijmegen, Netherlands
[8] Friedrich Alexander Univ Erlangen Nurnberg, Univ Klinikum Erlangen, Med Klin 1, Erlangen, Germany
[9] Friedrich Schiller Univ, Inst Microbiol, Jena, Germany
[10] German Canc Consortium DKTK, Partner Site Munich, Munich, Germany
[11] German Ctr Infect Res DZIF, Partner Site Munich, Munich, Germany
基金
欧洲研究理事会; 欧盟地平线“2020”;
关键词
Immune escape; immune evasion; host-pathogen interactions; fungal adaptation; filamentous growth; cell wall remodelling; FC-GAMMA; ALPHA-1-ANTITRYPSIN; INFLAMMASOME; RECOGNITION; PROTEIN; ESCAPE; ACTIVATION; IL-1-BETA; RECEPTOR; DECTIN-1;
D O I
10.1080/21505594.2024.2333367
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Our immune system possesses sophisticated mechanisms to cope with invading microorganisms, while pathogens evolve strategies to deal with threats imposed by host immunity. Human plasma protein alpha 1-antitrypsin (AAT) exhibits pleiotropic immune-modulating properties by both preventing immunopathology and improving antimicrobial host defence. Genetic associations suggested a role for AAT in candidemia, the most frequent fungal blood stream infection in intensive care units, yet little is known about how AAT influences interactions between Candida albicans and the immune system. Here, we show that AAT differentially impacts fungal killing by innate phagocytes. We observed that AAT induces fungal transcriptional reprogramming, associated with cell wall remodelling and downregulation of filamentation repressors. At low concentrations, the cell-wall remodelling induced by AAT increased immunogenic beta-glucan exposure and consequently improved fungal clearance by monocytes. Contrastingly, higher AAT concentrations led to excessive C. albicans filamentation and thus promoted fungal immune escape from monocytes and macrophages. This underscores that fungal adaptations to the host protein AAT can differentially define the outcome of encounters with innate immune cells, either contributing to improved immune recognition or fungal immune escape.
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页数:19
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